Aspetti ipnici e vegetativi dell'inibizione del controllo nervoso centrale della termogenesi nel ratto

The possibility to mimic hypomethabolic and hypothermic states like torpor or hibernation in non-hibernating animals may be useful in medical practice since the beneficial effects of deep hypothermia could be obtained without the concomitant elicitation of adverse autonomic compensatory responses. Until now, tentatives of induction of such states have been focused on the inhibition of cellular metabolism at systemic level but worked only in animals already able to enter torpor. Here we show a new approach, that involves the pharmacological blockade of the activity of the neurons within the Rostral Ventromedia Medulla (RVMM), a brainstem area that has been shown to be a key thermogenetic relay that controls the brown adipose tissue, the cutaneous blood vessels and the heart. In our experiment, six consecutive injections, aimed to block the thermogenetic drive by the activation of the GABAA receptors in RVMM neurons, induced a reversible deep hypothermia (21°C at nadir) state in free behaving rats exposed to 15°C ambient temperature. The hypothermic/hypometabolic state produced by prolonged inhibition of RVMM neurons strongly resembles the naturally occurring torpor, even in the EEG changes observed during and after the procedure. Like animals that spontaneously show hibernation or torpor, rats with the thermogentic drive blocked show a left-shift of all the EEG frequencies during the hypothermia, and a strong increase in EEG power spectrum after the return to thermoneutrality, in particular in the EEG Delta band (0.5-4.0 Hz) during NREM sleep. In conclusion, these results show that the selective pharmacological inhibition of a key brainstem area of the cold-defence pathway is sufficient in inducing a topor-like state in the rat, a species that does not enter torpor spontaneously. Such an approach may open new perspectives in the use of deep hypothermia in several medical conditions.